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Background: Cancer patients are at high risk for severe sepsis (SS) and septic shock (SSh) and delay to effective antimicrobial therapy (ABx) is strongly associated with increased mortality. Anti-pseudomonal beta-lactam intravenous monotherapy is equally effective and less toxic than combination therapy for uncomplicated neutropenic fever, but combination therapy may be superior for more severe disease. Methods: We implemented a clinical algorithm to simplify timely and effective empiric ABx and other resuscitative care to cancer outpatients with SS/SSh prior to hospital admission. Triple therapy with meropenem, tobramycin and linezolid or alternatives such as aztreonam for penicillin-allergic patients can be co-administered and provides broad coverage for resistant organisms typically encountered in this population. A pre-printed order form triggered dispensing of kits containing ABx, fluids and dexamethasone. We performed a retrospective cohort study to assess the impact of this strategy. Results: From 1/1/08 through 1/31/12, 162 patients met inclusion criteria. Median age was 53 (IQR: 42 – 63) years and 65% were male. The majority of patients (87%) had hematopoietic malignancies. 77 (48%) were hematopoietic stem cell transplant recipients and 80 (49%) were neutropenic. SSh was diagnosed in 25 patients (15%), SS in 46 (28%), sepsis in 72 (44%) alternative diagnosis in 6 (4%) and infection without systemic inflammatory response syndrome in 13 (8%). Median time from clinical encounter to ABx administration was 111 (IQR: 60 – 178) minutes, 93% had blood cultures drawn prior to ABx, 46% received dexamethasone and 99% had crystalloid infusion started before hospital transfer. De-escalation on hospital day 1 occurred in 95% of persons admitted. 44% of 25 persons with SSh received vasopressors. 71 persons (44%) had bacteremia and 18% of 93 isolates were multidrug resistant. Possible nephrotoxicity occurred in 7 patients. 30 day mortality was 6/160 (4%) including 3/71 (4%) with SS/SSh. For each hour delay to administer antibiotics, there was an18% increased risk of developing SSh or death within 30 days (95% CI: 4 – 34%), p=0.01. Conclusions: A program to simplify choice of aggressive empiric ABx among cancer patients presenting to an ambulatory clinic with suspected sepsis was associated with excellent survival in those with SS/SSh, without excessive adverse events or inappropriately long empiric ABx durations.